Isononyl acetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from SIDS Dossier.

Data source

Reference

Reference Type:

secondary source

Title:

n-butyl Acetate - SIDS Dossier

Author:

United Nations Environmental Programme (UNEP)

Year:

2008

Bibliographic source:

n-butyl Acetate - SIDS Dossier, United Nations Environmental Programme (UNEP), October 2008.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as metioned below

Principles of method if other than guideline:

Acute inhalation toxicity of N-butyl acetate (CAS no: 123-86-4) in rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-butyl acetate

EC Number:

204-658-1

EC Name:

N-butyl acetate

Cas Number:

123-86-4

Molecular formula:

C6H12O2

IUPAC Name:

N-butyl acetate

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): N-butyl acetate
- Molecular formula (if other than submission substance): C6H12O2
- Molecular weight (if other than submission substance): 116.16 g/mol
- Substance type: Organic
- Physical state: liquid
- Smiles : O(CCCC)C(C)=O
- InChI: 1S/C6H12O2/c1-3-4-5-8-6(2)7/h3-5H2,1-2H3

Specific details on test material used for the study:

- Name of test material (as cited in study report): N-butyl acetate
- Molecular formula (if other than submission substance): C6H12O2
- Molecular weight (if other than submission substance): 116.16 g/mol
- Substance type: Organic
- Physical state: liquid
- Smiles : O(CCCC)C(C)=O
- InChI: 1S/C6H12O2/c1-3-4-5-8-6(2)7/h3-5H2,1-2H3
- Purity >99.9%
- Impurities (identity and concentrations): <0.1%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel inhalation chambers
- Exposure chamber volume: 420 L
- Method of holding animals in test chamber:No data
- Source and rate of air:room air
- Method of conditioning air: infrared gas analyzer
- System of generating particulates/aerosols:
- Method of particle size determination: The test substance was metered onto a heated glass distillation column packed with glass beads and filtered, metered conditioned air was passed through the column to generate the vapor atmosphere.
- Treatment of exhaust air:Air changes were 12-14/hour.
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber concentrations were analysed by an infrared gas analyzer. The chamber atmosphere was checked for homogeneity and found to deviate less than 10% from the reference position and therefore was considered homogenous.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

6 h

Remarks on duration:

not specified

Concentrations:

0, 2000, 5000, or 8000 ppm

No. of animals per sex per dose:

Total = 24
3 male and 3 female rats – 0 ppm
3 male and 3 female rats – 2000 ppm
3 male and 3 female rats – 5000 ppm
3 male and 3 female rats – 8000 ppm

Control animals:

yes

Remarks:

Total = 6 (male and female)

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations: Clinical exams were conducted prior to exposure, immediately after exposure and daily thereafter for 5 days.
Weighing: Body weights were collected prior to exposure and daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights and histopathology.
Other: The oxygen content, airflow, temperature, humidity, and concentration were recorded every 30 minutes.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 8 000 000 mg/m³ air

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: No mortality was observed

Mortality:

At 8000 ppm – Some of the female animal was found dead at the post exposure observation time point.

Clinical signs:

other: During Exposure Period - At 0 ppm (Control)- No unusual clinical signs were noted during exposure in the control animals. At 2000 ppm - Minimal hypoactivity was observed during exposure from 3-6 hours in all the 2000-ppm exposure group animals. The 2000-p

Body weight:

All groups (including the Control Group) lost weight from Day 0 to Day 1, but regained weight from Day 1 to Day 4. However, the groups exposed to the test article lost more weight (from Day 0 to Day 1) than the Control group.

Gross pathology:

not specified

Other findings:

not specified

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LC50 was considered to be >8000 ppm (>8000000 mg/m3), when rat was exposed to N-butyl acetate for 6 hr.

Executive summary:

The acute inhalation toxicity study was conducted by using N-butyl acetateat the concentration of 0, 2000, 5000, or 8000 ppm for 6 hours in 4 groups of 3 male and 3 female of Sprague-Dawley rats. The inhalation exposures were conducted in 420 L stainless steel inhalation chambers and maintained at negative pressure relative to room air. The oxygen content, airflow, temperature, humidity, and concentration were recorded every 30 minutes. The test substance was metered onto a heated glass distillation column packed with glass beads and filtered, metered conditioned air was passed through the column to generate the vapor atmosphere. Air changes were 12 -14/hour. The presence of aerosols was checked for and determined not to be present. Chamber concentrations were analysed by an infrared gas analyzer. The chamber atmosphere was checked for homogeneity and found to deviate less than 10% from the reference position and therefore was considered homogenous. Nominal concentrations were also determined. The purity of the test substance was checked with gas chromatography with flame ionization detection and was found to be greater than 99.9%. The structure of the test substance was checked by mass spectrometry. Clinical exams were conducted prior to exposure, immediately after exposure and daily thereafter for 5 days. Body weights were collected prior to exposure and daily thereafter. During Exposure Period - All groups (including the Control Group) lost weight from Day 0 to Day 1, but regained weight from Day 1 to Day 4. However, the groups exposed to the test article lost more weight (from Day 0 to Day 1) than the Control group. During Exposure Period - At 0 ppm (Control) - No unusual clinical signs were noted during exposure in the control animals. At 2000 ppm - Minimal hypoactivity was observed during exposure from 3-6 hours and he animals responded to tapping on the side of the chamber (startle reflex stimuli). At 5000 ppm - Minimal sialorrhea and minor hypoactivity were observed within 30 minutes of exposure initiation. The severity of sialorrhea increased to moderate to severe by 1 hour and the degree of hypoactivity increased to moderate in all animals by 2 hours abd the animals had a decreased startle response to tapping stimuli beginning at 2 hours and continuing through the end of the exposure. At 8000 ppm – Moderate hypoactivity was noted at 30 minutes and this effect increased to severe hypoactivity accompanied by prostration by 2 hours in the female and 3 hours in the male animals. Minor to moderate sialorrhea and reduced response to startle stimuli were noted during the exposure in the animals. During the post exposure period - No test substance related clinical signs were noted in either the control or 2000-ppm groups. Decreased arousal and unkempt hair coat were noted in the 5000-ppm exposure group animals until Day 4 post exposure when they were all normal. Severely decreased arousal, hypothermia, and no responsiveness to touch stimuli were noted immediately post exposure in two of three rats in both the male and female 8000-ppm groups. The remaining male rat from the 8000-ppm group had moderately decreased arousal. Abnormal gait, incomplete extension at the tarsus, decreased arousal/alertness, and unkempt hair coat were noted in the male rats during the post exposure Days 1-4. The female rats were normal during post exposure Days 1-4. At 8000 ppm – Some of the female animal was found dead at the post exposure observation time point. Therefore, LC50 was considered to be >8000 ppm (>8000000 mg/m3), when rat was exposed to N-butyl acetate for 6 hr.